Gastroesophageal Reflux Disease, Gastroparesis
Conditions
Keywords
Gastroparesis, Gastroesophageal reflux disease, heartburn
Brief summary
The purpose of this study is to compare the blood drug levels of two prescribed medications, immediate-release omeprazole 40 mg powder and delayed-release omeprazole 40 mg capsule to determine which drug is better absorbed in patients with a slow stomach emptying (gastroparesis). Delayed-release omeprazole has a protective coating to prevent the drug omeprazole from being neutralized by stomach acid. Immediate-release omeprazole has sodium bicarbonate (antacid) which neutralizes the stomach acid, eliminating the need for a protective coating. Immediate-release omeprazole suspension may have a more rapid pharmacokinetic profile and greater overall drug absorption in gastroparesis.
Detailed description
Hypothesis: Immediate-release omeprazole suspension may have a more rapid pharmacokinetic profile and greater overall drug absorption in gastroparesis. This will result in shorter time to maximal drug concentration, greater maximal concentration, and greater total area under the curve of the concentration vs. time plot. Primary Objective: To compare the pharmacokinetics of omeprazole between immediate-release suspension and delayed-release capsules in patients with heartburn associated with gastroparesis. Study design: randomized, open-labeled, crossover treatment for 7 days with 10-14 days washout. Pharmacokinetic studies will be performed after 7 days on study drug.
Interventions
DRUGImmediate-release omeprazole
Immediate-release omeprazole 40 mg qam for 7 days
DRUGDelayed-release omeprazole
Delayed-release omeprazole 40 mg qam for 7 days
Sponsors
Bausch Health Americas, Inc.
University of Louisville
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Symptoms of heartburn \>2 days per week off antireflux therapy, defined by a burning feeling rising from the stomach or lower chest up towards the neck * Symptoms of gastroparesis \>1 month in duration, defined by nausea, vomiting, bloating, dyspepsia, early satiety, or effortless regurgitation. * Prior abnormal 4-hour gastric emptying scan within the past 3 years
Exclusion criteria
* History of esophageal or gastric surgery * Severe gastroparesis with any of the following: vomiting with dehydration requiring IV hydration, hospitalization, weight loss \>10 % pre-illness weight, requiring feeding jejunostomy tubes * Presence of gastric electrical stimulator * Symptoms of retching with vomiting more than 2 days per week * Diagnosis of diabetes * Disorders of small bowel motility (such as pseudo-obstruction or dumping syndrome) * Disorders of small bowel absorption * Diagnosis of gastric outlet, small bowel or colon mechanical obstruction * Diagnosis of acid hypersecretory syndrome * Disorders affecting proton pump inhibitor metabolism (such as liver failure) * Known allergy or side effects to proton pump inhibitor * Non-ambulatory patients: bed-ridden, nursing home resident, etc. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximal Omeprazole Concentration (Tmax) | 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment | Time to max concentration for Immediate release vs. Delayed release omeprazole |
| Maximal Concentration of Omerazole | 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment | Maximal concentration of immediate-release vs. delayed-release omeprazole |
| Area Under the Curve for Omeprazole Plasma Concentration | 0 to 5 hrs after the study drug was ingested on treatment day 7 | The area under the curve for omeprazole concentration-time curve for immediate release and delayed release omeprazole. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Curve for Omeprazole Plasma Concentration
The area under the curve for omeprazole concentration-time curve for immediate release and delayed release omeprazole.
Time frame: 0 to 5 hrs after the study drug was ingested on treatment day 7
Population: the AUC for each formulation were combined regardless of order given
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Immediate Release Arm | Area Under the Curve for Omeprazole Plasma Concentration | 3842 mg*h/mL | Standard Deviation 1618 |
| All Study Subjects Delayed Release Arm | Area Under the Curve for Omeprazole Plasma Concentration | 3745 mg*h/mL | Standard Deviation 2386 |
p-value: 0.95ANOVA
Primary
Maximal Concentration of Omerazole
Maximal concentration of immediate-release vs. delayed-release omeprazole
Time frame: 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment
Population: All subjects were included, regardless of which formulation they received first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Immediate Release Arm | Maximal Concentration of Omerazole | 1979 ng/mL plasma | Standard Deviation 832 |
| All Study Subjects Delayed Release Arm | Maximal Concentration of Omerazole | 1625 ng/mL plasma | Standard Deviation 921 |
Primary
Time to Maximal Omeprazole Concentration (Tmax)
Time to max concentration for Immediate release vs. Delayed release omeprazole
Time frame: 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment
Population: All subjects were included regardless of which formulation they received first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants Immediate Release Arm | Time to Maximal Omeprazole Concentration (Tmax) | 32 minutes | Standard Deviation 11 |
| All Study Subjects Delayed Release Arm | Time to Maximal Omeprazole Concentration (Tmax) | 97 minutes | Standard Deviation 46 |
p-value: <0.01paired t-tests